The purpose of this study is to determine wether pirfenidone is safe and effective in the treatment of pulmonary fibrosis with anti-myeloperoxydase (MPO) antibodies or pulmonary fibrosis with anti-MPO associated vasculitis.
Pulmonary fibrosis can be associated with Anti-Neutrophil Cytoplasmic Antibody (ANCA) directed against MPO or with anti-MPO associated vasculitis, leading to increased disability and poor prognosis. The pathophysiology of this association remains unclear. Conventional therapies used for the treatment of vasculitis manifestations are often disappointing for the treatment of pulmonary fibrosis. The main cause of death in patients with anti-MPO ANCA associated vasculitis and associated pulmonary fibrosis is the progression of pulmonary fibrosis. No treatment has demonstrated efficacy to stabilize or improve pulmonary fibrosis associated with anti-MPO associated vasculitis. Previous studies showed that Pirfenidone improves survival and pulmonary function in patients with idiopathic pulmonary fibrosis (IPF) and that Pirfenidone treatment is safe and well tolerated in IPF. Patients with anti-MPO associated vasculitis (or anti-MPO antibodies without vasculitis) and associated pulmonary fibrosis might benefit from the use of Pirfenidone. However, the efficacy and safety of pirfenidone in patients with anti-MPO associated vasculitis and associated pulmonary fibrosis has not been evaluated. This study was designed to assess the efficacy and safety of pirfenidone in patients with pulmonary fibrosis and anti-MPO ANCA associated vasculitis or anti-MPO antibodies without vasculitis.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
7
Pirfenidone at a dose of 2403 mg/day for 50 weeks, after a 2 weeks period of titration (801 mg/day for one week then 1602 mg/day for one week).
Cochin Hospital
Paris, France
Treatment efficacy measured by the absolute change in percent predicted forced vital capacity (%FVC)
Treatment efficacy at Week 52 measured by the absolute change from baseline to Week 52 in percent predicted forced vital capacity (%FVC) : * Patients with progressive disease will be defined as absolute decline of 10% or more in %FVC. Missing values or death will be also considered as progressive. * Patients with non-progressive disease will be defined as improvement or no decline in %FVC or a decline of %FVC\<10%.
Time frame: 52 weeks
Adverse Events (AE)
Safety parameters reported in the period from baseline to 28 days after the last dose of the study drug: * Treatment-emergent AEs * Treatment-emergent Serious Adverse Events (SAE) * Treatment emergent Adverse Event of Special Interest (AESI) * Treatment-emergent treatment-related AEs * Treatment-emergent treatment-related SAEs * Treatment emergent related AESIs * AEs leading to early discontinuation of study treatment * Treatment-emergent deaths * Cause of death * Treatment-emergent changes in clinical laboratory findings * Vital signs
Time frame: 56 weeks corresponding to 28 days after the last dose of study drug
Treatment efficacy measured by the absolute change in percent predicted forced vital capacity (%FVC)
Treatment efficacy at Week 24 measured by the absolute change from baseline to Week 24 in percent predicted forced vital capacity (%FVC) : * Patients with progressive disease will be defined as absolute decline of 10% or more in %FVC. Missing values or death will be also considered as progressive. * Patients with non-progressive disease will be defined as improvement or no decline in %FVC or a decline of %FVC\<10%.
Time frame: 24 weeks
Relative change in in percent predicted forced vital capacity
Relative change from baseline to Week 52 in percent predicted forced vital capacity (%FVC)
Time frame: 52 weeks
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Absolute change in in percent predicted forced vital capacity
Relative and absolute change from baseline to Week 52 in percent predicted forced vital capacity (%FVC)
Time frame: 52 weeks
Relative change in in percent predicted forced vital capacity
Relative and absolute change from baseline to Week 24 in percent predicted forced vital capacity (%FVC)
Time frame: 24 weeks
Absolute change in in percent predicted forced vital capacity
Relative and absolute change from baseline to Week 24 in percent predicted forced vital capacity (%FVC)
Time frame: 24 weeks
Six minute walk test (6MWT) distance
Change from Baseline to Week 52 in the six minute walk test (6MWT) distance
Time frame: 52 weeks
Six minute walk test (6MWT) distance
Change from Baseline to Week 24 in the six minute walk test (6MWT) distance
Time frame: 24 weeks
Carbon Monoxide Diffusing Capacity (%DLCO)
Change from Baseline to Week 52 in the percent predicted Carbon Monoxide Diffusing Capacity (%DLCO)
Time frame: 52 weeks
Carbon Monoxide Diffusing Capacity (%DLCO)
Change from Baseline to Week 24 in the percent predicted Carbon Monoxide Diffusing Capacity (%DLCO)
Time frame: 24 weeks
Progression-free survival
Progression-free survival defined as the time to the first occurrence of any one of the following: a confirmed decrease of 10 percentage points or more in %FVC, a confirmed decrease of 15 percentage points or more in %DLCO, or death.
Time frame: 52 weeks
Dyspnea
Change from Baseline to Week 52 in dyspnea as measured by the New York Heart Association classification, the modified Borg scale and by the Saint-George's Respiratory Questionnaire (SGRQ).
Time frame: 52 weeks
Chest CT-scan
Change in Chest-CT scan abnormalities at Week 52 (evaluated after a centralized blinded review of the chest CT-scans).
Time frame: 52 weeks
Quality of Life assessed by the Health Assessment Questionnaire (HAQ)
Time frame: 52 weeks
Quality of Life assessed by the Short Form-36 (SF-36)
Time frame: 52 weeks